Preclinical evaluation of the biodistribution, biological activity and therapeutic efficacy of recombinant TAT?-CDKL5 protein in models of CDKL5 Deficiency Disorder

The project will evaluate the biodistribution, biological activity and therapeutic efficacy of recombinant TAT?-CDKL5 protein in cellular and mouse models of CDKL5 Deficiency Disorder. Cellular studies will assess protein uptake, localization and persistence, together with effects on neuronal survival and maturation. Mouse studies will examine brain distribution, neuronal localization and pharmacodynamic responses to identify a dosing regimen for efficacy testing. Treatment effects will be assessed through behavioural testing and biochemical, histological and morphometric analyses, with particular attention to dendritic and synaptic alterations. Integrated findings will support the evaluation of the therapeutic potential of protein replacement therapy.